PROJECT ABSTRACT The Georgia Clinical and Translational Science Alliance (Georgia CTSA) is a compelling partnership of Emory University, Morehouse School of Medicine (MSM), the Georgia Institute of Technology and the University of Georgia (UGA). The KL2 Program is an essential component of the Georgia CTSA and will respond to these critical needs to train a new and diverse generation of clinical and translational research (CTR) investigators who will carry out high impact research and translate new discoveries to improve health. The KL2 Program is focused on enhancing the career development of a diverse and talented group of junior faculty (Instructor or Assistant Professor level) with either PharmD, PhD and/or MD degrees at the Georgia CTSA partner institutions. Dr. Dunn will use the Georgia CTSA KL2 Program to obtain personalized training by completing carefully planned didactic coursework, individualized instruction, attending seminars and conferences, and completing supervised research experiences under the guidance of a mentoring team of seasoned investigators with expertise in depression physiology, neuroendocrine and stress physiologic pathways, biostatistical microbiome analysis, and translational research methods. The objective of this proposal is to explore biological pathways underpinning Postpartum depression (PPD)-the most common peripartum mood disorder affecting more than 500,000 women in the US annually. The latest evidence suggests that several biological mechanisms influence PPD symptoms including altered immune and inflammatory pathways. One area of scientific inquiry that has been found to influence immune and inflammatory pathways that has also emerged as a key depression biomarker and target for therapeutic intervention in non-pregnant human and animal models is the brain-gut microbiota axis (BGMA), an unexplored area of research within the context of PPD. Recent findings have shown that individuals with major depression demonstrate a different gut microbial composition than non-depressed individuals. Gut associated microbes are known to leak across the gut initiating inflammatory immune reactions in the gut mucosa as well as the host systemic inflammatory response. However, neither gut microbiome composition or gut leakiness ? or their contribution to host inflammation --have been explored in the context of PPD symptoms. Thus, to investigate the contribution of the BGMA on postpartum depressive symptoms in accordance with clinical postpartum care guidelines (within the first 3 weeks postpartum), DSM-V criteria (prenatal onset/ within 4 weeks following delivery), and recent Georgia maternal mortality data findings, we will prospectively enroll a pilot sample of 60 women at 3 weeks postpartum. We will investigate the relationships between the gut microbiome composition, markers of intestinal barrier dysfunction (LPS binding protein), systemic inflammatory markers (cytokines), and postpartum depressive symptoms. We will also measure and control for factors that have the potential to disturb the BGMA (diet, sleep, stress, and medications).